Clinical Insights: Integrating Durvalumab Into Non–Muscle-Invasive Bladder Cancer Care

At a Clinical Insights discussion coinciding with the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Oncology Brothers podcast cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, were joined by Shilpa Gupta, MD, of Cleveland Clinic; Amit Patel, MD, of Duly Health and Care; and Neal Shore, MD, FACS, of the Carolina Urologic Research Center, to discuss the recent FDA approval of durvalumab plus BCG for patients with high-risk NMIBC based on findings from the phase 3 POTOMAC trial.

POTOMAC Establishes Durvalumab Plus BCG as a New Standard Option

Dr. Shore reviewed the current risk stratification approach for NMIBC, which categorizes patients as low-, intermediate-, or high-risk based on tumor grade, tumor stage, and the presence of carcinoma in situ (CIS). High-risk disease includes high-grade Ta tumors, T1 tumors involving the lamina propria, and CIS, all of which carry substantial risks of recurrence and progression to muscle-invasive disease. 

For decades, induction and maintenance BCG have been the standard of care for patients with high-risk NMIBC. Although BCG reduces recurrence and progression rates, significant unmet need remains. Dr. Patel noted that recurrence rates may approach 70% within 5 years, while progression rates can reach 25% to 50% in patients with very high-risk features such as extensive T1 disease, concomitant CIS, or variant histology.

Dr. Gupta reviewed the design of the phase 3 POTOMAC trial, which enrolled more than 1000 patients with treatment-naive high-risk NMIBC. Patients were randomized to receive standard BCG induction and maintenance, durvalumab plus BCG induction and maintenance, or durvalumab plus BCG induction alone. The primary analysis compared durvalumab combined with induction and maintenance BCG against standard BCG therapy, with recurrence-free survival serving as the primary end point.

The study met its primary objective, demonstrating a significant improvement in recurrence-free survival with the addition of durvalumab. Dr. Gupta highlighted a hazard ratio of 0.68, indicating a meaningful reduction in recurrence risk. Although overall survival data remain immature, investigators have observed encouraging findings related to cystectomy-free survival and other clinically relevant outcomes.

Additional analyses presented at major meetings have continued to support the efficacy of the combination. Dr. Shore noted that rates of high-risk recurrence, BCG-unresponsive disease, persistent CIS, and progression to muscle-invasive bladder cancer were consistently lower in the durvalumab-containing arm. Importantly, no unexpected safety concerns emerged, and no grade 5 treatment-related adverse events were reported.

Identifying Appropriate Candidates and Managing Toxicities

Much of the discussion centered on which patients are most likely to benefit from the addition of durvalumab. Although the approved indication encompasses high-risk NMIBC broadly, panelists suggested that patients with the greatest risk of recurrence and progression may be particularly attractive candidates. Dr. Patel indicated that patients with extensive T1 disease, concomitant CIS, or other very high-risk features may be prioritized initially in clinical practice. However, in the absence of validated predictive biomarkers, patient selection largely depends on clinical judgment, risk assessment, and shared decision-making discussions.

Adding immunotherapy introduces considerations that have traditionally fallen outside the scope of routine NMIBC management. Dr. Gupta emphasized that while most patients tolerate immune checkpoint inhibitors well, clinicians must remain vigilant for immune-related adverse events, including endocrinopathies, pneumonitis, hepatitis, colitis, neurologic toxicities, myocarditis, and other serious complications.

Because the treatment is being delivered in a potentially curative setting, maintaining a favorable balance between efficacy and toxicity is particularly important. Patients should be counseled regarding both common and rare immune-mediated toxicities and encouraged to promptly report any new symptoms. Dr. Gupta stressed that early recognition and intervention remain critical to minimizing complications and preserving long-term outcomes.

Multidisciplinary Care and Practical Implementation Challenges

The approval of durvalumab plus BCG raises important questions regarding how treatment will be implemented across different practice settings. Historically, most patients with NMIBC have been managed exclusively by urologists, but panelists agreed that broader collaboration with medical oncologists will likely become increasingly important. Dr. Shore suggested that larger integrated practices may have the infrastructure to administer and monitor immunotherapy within urology clinics, although he expects most patients will continue to be referred to medical oncologists for systemic treatment. Dr. Patel similarly emphasized the importance of educating community urologists about patient selection, treatment outcomes, and referral pathways while strengthening relationships with local oncology practices.

The panel also discussed practical issues such as ongoing BCG shortages, which continue to affect treatment delivery in some regions. Although no definitive data exist regarding optimal management when BCG availability is interrupted, panelists generally agreed that continuing durvalumab during temporary BCG shortages may be reasonable. At the same time, they emphasized that clinicians should avoid reducing or omitting BCG simply because immunotherapy has been added, given BCG’s critical role in disease control.

The panel agreed that as the treatment landscape continues to evolve, the POTOMAC data represent a significant advance for patients with high-risk NMIBC. The approval also signals a growing need for coordinated care between urologists and medical oncologists, ensuring that patients receive both the benefits of novel therapies and the specialized expertise required to manage them effectively.